Clinical Trial: Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Phase I Trial of Lithium and Tretinoin for Treatment of Non-Promyelocytic Acute Myeloid Leukemia in Patients Intolerant or Relapsed/Refractory to Standard Chemotherapy.
Brief Summary: This phase I trial studies the side effects and best dose of tretinoin when given together with lithium carbonate in treating patients with relapsed or refractory acute myeloid leukemia. Lithium carbonate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Tretinoin may help [type of cancer] cells become more like normal cells, and to grow and spread more slowly. Giving lithium carbonate together with tretinoin may kill more cancer cells
Detailed Summary:
PRIMARY OBJECTIVES:
I. To determine the safety and maximum tolerated dose of the combination of tretinoin with lithium carbonate in subjects with non promyelocytic acute myeloid leukemia.
SECONDARY OBJECTIVES:
I. To describe the dose limiting toxicities associated with the combination of lithium (lithium carbonate) and tretinoin.
II. To determine the ability of lithium to inhibit glycogen synthase kinase-3 (GSK3) activity in circulating acute myeloid leukemia (AML) cells and to enhance the retinoic acid receptor expression.
III. To determine the ability of lithium and tretinoin to induce differentiation and/or growth inhibition of AML cells.
IV. To determine the response rate of acute myeloid treatment to treatment with the combination of Tretinoin and Lithium.
OUTLINE: This is a dose-escalation study of tretinoin.
Patients receive tretinoin orally (PO) every 12 hours on days 1-7 and 15-21 and lithium carbonate PO three times daily (TID) on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Sponsor: Paolo Caimi, MD
Current Primary Outcome: Maximum tolerated dose of tretinoin when given together with lithium carbonate, defined as the dose level immediately below that at which at least 2/6 subjects experience dose-limiting toxicity (DLT), graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 28 days ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Case Comprehensive Cancer Center
Dates:
Date Received: March 26, 2013
Date Started: April 30, 2013
Date Completion:
Last Updated: April 25, 2017
Last Verified: April 2017
